N-Methyl-d-aspartate receptor mediated toxicity in nonneuronal cell lines: characterization using fluorescent measures of cell viability and reactive oxygen species production

2000 ◽  
Vol 77 (2) ◽  
pp. 163-175 ◽  
Author(s):  
Norifusa J. Anegawa ◽  
Rodney P. Guttmann ◽  
Elfrida R. Grant ◽  
Rene Anand ◽  
Jon Lindstrom ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Cell Lines ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Aspartate Receptor ◽  
Species Production

Mimosine Induces Apoptosis through Metal Ion Chelation, Mitochondrial Activation and Reactive Oxygen Species Production in Human Leukemic Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4481-4481 ◽  
Author(s):  
Maher Hallak ◽  
Alexander Dvilansky ◽  
Ofer Shpilberg ◽  
Itai Levi ◽  
Julia Mazar ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Lines ◽  
Metal Ion ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
G1 Arrest ◽  
Oxygen Species ◽  
Effect Of Mimosine ◽  
Apoptotic Effect ◽  
Species Production

Abstract Mimosine, a non-protein amino acid, acts as a reversible inhibitor of DNA replication, and is widely used to synchronize cells at G1 phase of the cell cycle. We tested the possibility that mimosine might have an apoptotic effect on two types of AML cells: the monoblastic U-937 and the promyelocytic HL-60 cell lines. We show that mimosine induces apoptosis in both cell lines, with U-937 cells being more sensitive. The apoptotic effect of mimosine was antagonized by the addition of exogenous iron, indicating that it may act through iron chelation. Its mode of action was thus compared to that of desferrioxamine (DFO), a therapeutic iron chelating agent. Mimosine and DFO differed in their sensitivity to the suppressive effect of exogenous sources of iron in the form of hemin and ferrous sulfate suggesting different targets of action. Addition of another metal ion cupric sulfate was also able to antagonize the apoptotic effect of mimosine, undermining the notion that apoptosis is mediated through inhibition of ribonucleotide reductase, since this enzyme is solely dependent on iron for its activity. Moreover, when higher concentrations of iron were added to mimosine, cell death shifted from apoptosis to necrosis. Induction of apoptosis by both mimosine and DFO caused an early reduction in mitochondrial transmembrane potential and increase in caspase-3 activity, while only mimosine induced oxidative stress. In summary, our results imply that besides its known effect on DNA synthesis and G1 arrest, mimosine also activates apoptosis through an intrinsic pathway as well as reactive oxygen species production and thus elicits its anticancer effect by multiple pathways.

scholarly journals Cytotoxic effect of celastrol alone or in combination with paclitaxel on anaplastic thyroid carcinoma cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769836 ◽  
Author(s):  
Si Hyoung Kim ◽  
Jun Goo Kang ◽  
Chul Sik Kim ◽  
Sung-Hee Ihm ◽  
Moon Gi Choi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Thyroid Carcinoma ◽  
Cell Viability ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Protein Levels ◽  
Species Production

The influence of celastrol alone or in combination with paclitaxel on survival of anaplastic thyroid carcinoma cells was investigated. In 8505C and SW1736 cells, after treatment of celastrol, cell viability decreased, and cytotoxic activity increased. The protein levels of heat shock protein (hsp) 90, hsp70, Bax, death receptor 5, cleaved caspase-3, cleaved poly (ADP-ribose) polymerase, phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-c-Jun N-terminal kinase (JNK) were elevated, and those of Bcl2, phospho-nuclear factor-kappaB (NF-κB), and total and phospho-Akt were reduced. The endoplasmic reticulum stress markers expression and reactive oxygen species production were enhanced. In celastrol-treated cells, N-acetylcysteine increased cell viability and phospho-NF-κB protein levels, and decreased reactive oxygen species production and cytotoxic activity. The protein levels of cyclooxygenase 2, phospho-ERK1/2, phospho-JNK and Bip were diminished. After treatment of both celastrol and paclitaxel, compared with paclitaxel alone, cell viability and the percentage of viable cells were reduced, and death rate and cytotoxic activity were elevated. The protein levels of phospho-ERK1/2, phospho-JNK, Bip, and cyclooxygenase 2, and reactive oxygen species production were enhanced. All of the Combination Index values calculated by Chou–Talalay equation were lower than 1.0, implying the synergism between celastrol and paclitaxel in induction of cell death. In conclusion, our results suggest that celastrol induces cytotoxicity through involvement of Bcl2 family proteins and death receptor, and modulation of phospho-NF-κB, Akt, and mitogen-activated protein kinase in association with endoplasmic reticulum stress and reactive oxygen species production in anaplastic thyroid carcinoma cells. Moreover, celastrol synergizes with paclitaxel in induction of cytotoxicity in anaplastic thyroid carcinoma cells.

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